The major objective of this proposal is to develop animal models of disease by inducing trace element deficiencies and to use these models to elucidate the biochemial basis of the pathology. Copper deficiency produces arterial disease simulating dissecting aneurysms, lung pathology simulating pulmonary emphysema and a central nervous system disorder simulating Parkinson's disease. Lysyl oxidase, a copper metalloenzyme which plays a key role in crosslinking elastin and collagen in arteries and lungs will be characterized as to substrate specificity, natural inhibitors and stoichiometry of the reactions it catalyzes. An attempt will be made to improve and standardize the assay. The catecholamine and tyrosine hydroxylase concentrations in copper deficient brain are decreased. The most affected areas will be delineated and the role of copper in the activation of tyrosine hydroxylase will be explored. Zinc deficiency decreases appetite and produces a pathology of pregnancy analogous to that of essential fatty acid deficiency and of prostaglandin inhibitors. The mechanism of appetite control will be investigated by measurement of neurotransmitters in the hypothalamus and transport of their amino acid precursors. The relation of zinc to membranes and particularly its role in prostaglandin metabolism will be investigated.